What are the causes and treatments of hyponatremia (low sodium levels)?

From the Guidelines

Hyponatremia should be treated based on its severity, symptoms, and underlying cause, with the goal of correcting serum sodium levels while avoiding osmotic demyelination syndrome and other complications, as recommended by the most recent guidelines 1.

Treatment Approach

The treatment of hyponatremia depends on whether it is hypovolemic, euvolemic, or hypervolemic.

• For hypovolemic hyponatremia, fluid resuscitation with saline solution is necessary, along with correction of the underlying cause, such as discontinuation of diuretics or treatment of gastrointestinal losses 1.
• For euvolemic hyponatremia, treatment is based on the specific underlying cause, such as SIADH, where vasopressin receptor antagonists like tolvaptan may be used 1.
• For hypervolemic hyponatremia, especially in patients with liver cirrhosis, treatment involves fluid restriction, reduction or discontinuation of diuretics, and administration of hyperoncotic albumin or vasopressin receptor antagonists like tolvaptan 1.

Correction Rate

The correction rate of serum sodium should not exceed 8-10 mmol/L in 24 hours to avoid osmotic demyelination syndrome, with a goal of increasing sodium by 4-6 mmol/L in the first 24 hours for severe symptomatic cases 1.

Medications

Medications such as loop diuretics (e.g., furosemide), vasopressin receptor antagonists (e.g., tolvaptan), and salt tablets may be used based on the underlying cause and clinical presentation of hyponatremia 1.

Monitoring

Regular monitoring of serum sodium levels is crucial, especially in severe cases, to avoid overcorrection and to adjust treatment as necessary, typically every 2-4 hours initially 1.

Underlying Cause

Addressing the underlying cause of hyponatremia, whether it's medications, heart failure, liver disease, or endocrine disorders, is essential for effective management and prevention of recurrence 1.

From the FDA Drug Label

14 CLINICAL STUDIES 14. 1 Hyponatremia In two double-blind, placebo-controlled, multi-center studies (SALT-1 and SALT-2), a total of 424 patients with euvolemic or hypervolemic hyponatremia (serum sodium <135 mEq/L) resulting from a variety of underlying causes (heart failure, liver cirrhosis, syndrome of inappropriate antidiuretic hormone [SIADH] and others) were treated for 30 days with tolvaptan or placebo, then followed for an additional 7 days after withdrawal.

The primary endpoint for these studies was the average daily AUC for change in serum sodium from baseline to Day 4 and baseline to Day 30 in patients with a serum sodium less than 135 mEq/L. Compared to placebo, tolvaptan caused a statistically greater increase in serum sodium ( p <0. 0001) during both periods in both studies

Tolvaptan is effective in treating hyponatremia. The studies showed a statistically significant increase in serum sodium levels in patients treated with tolvaptan compared to placebo.

• The effects of tolvaptan were seen across all disease etiology subsets, including CHF, cirrhosis, and SIADH/other.
• Tolvaptan also reduced the need for fluid restriction in patients with hyponatremia. The results of the studies support the use of tolvaptan in the treatment of hyponatremia, as evidenced by the significant increase in serum sodium levels and reduction in need for fluid restriction 2.

From the Research

Definition and Prevalence of Hyponatremia

• Hyponatremia is defined as a serum sodium concentration <135mmol/l 3, 4
• It is the most common electrolyte disorder, affecting approximately 5% of adults and 35% of hospitalized patients 3
• Hyponatremia can lead to a wide spectrum of clinical symptoms, from mild to severe or even life-threatening, and is associated with increased mortality, morbidity, and length of hospital stay 3, 4

Causes and Classification of Hyponatremia

• Hyponatremia most commonly results from water retention 3
• It can be classified into three categories based on fluid volume status: hypovolemic hyponatremia, euvolemic hyponatremia, and hypervolemic hyponatremia 3
• The approach to managing hyponatremia should consist of treating the underlying cause 3

Symptoms and Signs of Hyponatremia

• Symptoms and signs of hyponatremia range from mild and nonspecific (such as weakness or nausea) to severe and life-threatening (such as seizures or coma) 3
• Symptom severity depends on the rapidity of development, duration, and severity of hyponatremia 3
• Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 3

Treatment of Hyponatremia

• Urea and vaptans can be effective treatments for the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects 3
• Vasopressin receptor antagonists are promising new therapeutic options for the treatment of hyponatremia, particularly for euvolemic and hypervolemic hyponatremia 5, 6, 7
• Hypertonic saline is reserved for patients with severely symptomatic hyponatremia, and should be used with caution to avoid overly rapid correction of hyponatremia 3
• The goal of treatment is to increase the serum sodium level by 4-6 mEq/L within 1-2 hours, but by no more than 10 mEq/L within the first 24 hours 3